7u4t

Structural highlights

Disease

VPP1_HUMAN Non-specific syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

VPP1_HUMAN Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that transports protons across cellular membranes. V-ATPase is responsible for the acidification of various organelles, such as lysosomes, endosomes, the trans-Golgi network, and secretory granules, including synaptic vesicles (PubMed:33065002, PubMed:33833240, PubMed:34909687). In certain cell types, can be exported to the plasma membrane, where it is involved in the acidification of the extracellular environment (By similarity). Required for assembly and activity of the vacuolar ATPase (By similarity). Through its action on compartment acidification, plays an essential role in neuronal development in terms of integrity and connectivity of neurons (PubMed:33833240).[UniProtKB:P32563][UniProtKB:Q29466]^{[1] [2] [3]}

See Also

• ATPase 3D structures

References

1. ↑ Wang L, Wu D, Robinson CV, Wu H, Fu TM. Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly. Mol Cell. 2020 Nov 5;80(3):501-511.e3. PMID:33065002 doi:10.1016/j.molcel.2020.09.029
2. ↑ Aoto K, Kato M, Akita T, Nakashima M, Mutoh H, Akasaka N, Tohyama J, Nomura Y, Hoshino K, Ago Y, Tanaka R, Epstein O, Ben-Haim R, Heyman E, Miyazaki T, Belal H, Takabayashi S, Ohba C, Takata A, Mizuguchi T, Miyatake S, Miyake N, Fukuda A, Matsumoto N, Saitsu H. ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H(+)-ATPases is essential for brain development in humans and mice. Nat Commun. 2021 Apr 8;12(1):2107. PMID:33833240 doi:10.1038/s41467-021-22389-5
3. ↑ Bott LC, Forouhan M, Lieto M, Sala AJ, Ellerington R, Johnson JO, Speciale AA, Criscuolo C, Filla A, Chitayat D, Alkhunaizi E, Shannon P, Nemeth AH, Angelucci F, Lim WF, Striano P, Zara F, Helbig I, Muona M, Courage C, Lehesjoki AE, Berkovic SF, Fischbeck KH, Brancati F, Morimoto RI, Wood MJA, Rinaldi C. Variants in ATP6V0A1 cause progressive myoclonus epilepsy and developmental and epileptic encephalopathy. Brain Commun. 2021 Oct 18;3(4):fcab245. PMID:34909687 doi:10.1093/braincomms/fcab245
4. ↑ Wang L, Wu D, Robinson CV, Fu TM. Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining. Proc Natl Acad Sci U S A. 2022 Aug 30;119(35):e2203742119. PMID:35994636 doi:10.1073/pnas.2203742119